The overall objective of this proposal is to evaluate the relative importance of mechanical factors within the myocardium, and hemodynamic aspects of the coronary circulation, in control of regional and transmural distribution of myocardial perfusion. The basis for quantification of these factors will be the simultaneous measurement of regional myocardial structure, perfusion and coronary artery anatomy. The approach is based on the use of a unique imaging device, the Dynamic Spatial Reconstructor (DSR). The DSR is a multiple x-ray source CAT scanner which differs from commercially available CT scanners in that it scans a volume instead of a slice, scans the volume in stop action and repeats the scan 60 times per second so that the angiographic delineation of dynamic functional geometry of the heart wall and coronary arterial tree can be evaluated simultaneously. Direct confirmation of the location and extent of the spatial distribution of myocardial perfusion, as judged by postmortem angiogram and distribution of radiolabelled microspheres, will be sought to establish accuracy of the DSR-based techniques. Three phases are to be executed in sequence. In Phase I the specific DSR-based angiographic and finite element analysis techniques will be developed and evaluated in experimental animals. In Phase II the role of physiological mechanical factors such as heart rate, afterload, and coronary vasodilatation in myocardial perfusion distribution will be evaluated. In Phase III the role of pathophysiological states such as myocardial hypertrophy, aortic valve insufficiency and coronary artery stenosis will be evaluated using the techniques developed. The significance of this proposal is that multiple interactive pathophysiological processes involved in myocardial perfusion can be evaluated simultaneously and that there is a strong possibility that only a single intravenous injection of relatively small volumes of roentgen contrast agent will be required for a detailed DSR-based study. This minimally invasive procedure may form the basis for investigation of subclinical disease states in humans.